High-performance liquid chromatography is a technic that has recently been applied to the diagnosis of hemoglobinopathies and thalassemias. Its advantages over other methods include increased sensitivity, resolution and simplicity, as well as speed. In this report, the authors present an HPLC procedure that uses a weak cation exchange column and a gradient elution system for the diagnosis of hemoglobinopathies and thalassemias. The authors illustrate the utility of this procedure by reporting three cases in which the technic enabled them to make the correct diagnosis, which by traditional methods would have been missed or equivocal.